Sensor with overcoating and process for making same

ABSTRACT

A sensor comprising a sensing element capable of sensing a component in an aqueous medium and an overcoating at least partially covering the sensing element. The overcoating comprises a water insoluble, component permeable, cross-linked cellulosic material and an effective amount of an opaque agent.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation in part of U.S. patent applicationSer. No. 853,460, filed Apr. 18, 1986, and now abandoned, entitled,"Optical Sensor"; U.S. patent application Ser. No. 917,913, filed Oct.10, 1986, now U.S. Pat. No. 4,798,738, entitled, "Improved Microsensor";and U.S. patent application Ser. No. 917,912, filed Oct. 10, 1986,entitled, "Improved Gas Sensor". The entire disclosure of each of theseapplications is herein incorporated by reference.

BACKGROUND OF INVENTION

This invention is directed to overcoatings for sensors and processes forpreparing these overcoated sensors.

In the above-mentioned patent applications there are described certainsensors and/or sensing systems for determining blood constituents.Typically of interest would be the determination of the concentration ofgases (partial pressure of gases), such as oxygen and carbon dioxide, ofhydrogen ions (pH), of other electrolytes, of glucose and the like inthe blood. These provide useful parameters for assessment of certainphysiological conditions of a patient.

The above-noted patent applications provide teachings for theconstruction of "sensors". These sensors are preferably of asufficiently small size to be used directly in vivo in a patient. Thiscontributes to monitoring the condition of the patient on a continuousbasis, as opposed to older known procedures which required theextraction of a blood sample for determination in a laboratory of theconstituents of interest in the blood.

Certain of the sensors of these patent applications utilize opticalindicators, in particular fluorescence indicators, having an opticalsurface. Typically, a matrix material containing a fluorescent dye isloaded onto the optical surface of an optical fiber. Interaction of thedye with the component to be sensed is monitored utilizing opticalsignals carried by the optical fibers.

It would be advantageous to provide a durable sensor which has nosubstantial or significant detrimental effect of the patient beingmonitored.

SUMMARY OF THE INVENTION

This invention provides for overcoated sensors, probes which includes aplurality or a bundle of sensors which are overcoated, and processes forpreparing the same. The sensors including the overcoatings areeffective, often more effective and useful because of the inclusion ofthe overcoatings.

This can advantageously be achieved in a coating for a sensing elementwhich includes a water insoluble component permeable, cross-linkedcellulosic material and an effective amount of an opaque agent. By"component permeable" is meant that the overcoating is permeable to thecomponent which is being sensed by the sensing element of the sensor.

The opaque agent can be distributed throughout the overcoating or theopaque agent can be placed on the sensing element and covered with theovercoating.

The present sensor includes a sensing element capable of sensing acomponent in an aqueous medium. The sensing element may be ofconventional and well known design and construction. Sensing elementsdisclosed in the above-noted patent applications are useful in thepresent invention. Preferably, the sensing element is chosen fromoptical indicators and electro-chemical indicators, with the opticalindicators being particularly useful. The useful optical indicatorsinclude both fluorescence indicators and absorbance indicators, with thefluorescence indicators being especially useful.

The optical indicators function by modifying a light signal, e.g., in anoptical fiber, in response to the presence of a certain component, e.g.,in an aqueous medium. For example, fluorescence indicators often includea de which is sensitive or responsive to a component. This dye can beplaced on the tip of an optical fiber and exposed to the aqueous mediumcontaining the component of interest. By monitoring the light signalsfrom the dye tipped optical fiber, the concentration or partial pressureof the component in the aqueous medium can be determined.

Any aqueous medium may be analyzed using the present sensors or probes.However, the present system is particularly useful for analyzingbiological or bodily fluids, such as blood, saliva and the like in vivo,e.g., in a human health care patient. The system is especially useful inanalyzing blood.

One important feature of the present overcoating is that of strength ordurability. For example, if, as is preferred, the present sensor o probeis to be placed in the cardiovascular system of a human patient tomonitor one or more components in the patient's blood, the overcoatingshould have sufficient strength to remain in tact during such service.On the other hand, the overcoating is to be permeable to the componentor components being sensed by the sensing element or elements to allowthe component or components of interest to access the sensing element orelements.

Cellulose-containing overcoatings are water insoluble and have a degreeof both strength and permeability. However, improvements in at leastone, preferably both, of these properties would be highly beneficial.

It has been found that an overcoating containing a crosslinked cellulosematerial has useful strength properties. Sensors and probes with suchovercoatings are useful in the above-noted in vivo blood analysisservice. The component permeability of the cross-linked cellulosecontaining overcoating can be advantageously affected by using one ormore permeability enhancing agents during the formation of theovercoating, as is described.

The overcoated sensors of the present invention can be used to sense anysuitable component is an aqueous medium. Such components include, forexample, gases, hydrogen ions, other electrolytes and glucose. Gases,such as oxygen and carbon dioxide, and hydrogen ions (often representedby pH) are very suitable to be analyzed or monitored by the presentsystem, particularly when the aqueous medium is blood.

Opaque agents are useful in the present invention to perform one or moreof the following: provide beneficial sensing element isolation; andreduce fluorescent dye migration into the sensing element.

When fluorescent dyes are employed, it is preferred to select the opaqueagent from dye adsorptive opaque agents and dye non-adsorptive opaqueagents. By "dye adsorptive opaque agents" is meant those agents whichare capable of physically absorbing or adsorbing one or more of thefluorescent dyes used in a given sensor or probe. Examples of dyeadsorptive opaque agents include carbon black, other carbon based opaqueagents, and the like and mixtures thereof. Carbon black is aparticularly useful dye adsorptive opaque agent. By "dye non-adsorptiveopaque agents" is meant those agents which are substantially not capableof physically absorbing or adsorbing one or more of the fluorescent dyesused in a given sensor or probe. Examples of dye non-adsorptive opaqueagents include ferric oxide, metallic phthalocyanines and mixturesthereof. Included among the metallic phthalocyanines useful in thepresent invention as opaque agents are phthalocyanines of the followingmetals: copper, iron, cobalt, lithium, magnesium, nickel, zinc,vanadium, manganese, sodium and mixtures thereof. A particularly usefuldye non-adsorptive opaque agent is copper phthalocyanine.

The present invention further involves a process for forming anovercoating of a coating material on a sensing element. In this process,the sensing element is contacted with a composition containing a solventand a soluble (in the solvent) cellulosic coating material or a soluble(in the solvent) precursor of a cellulosic coating material to form acomposition coated sensing element. The composition coated sensingelement is treated, e.g., as discussed hereinafter, to form or generatea cellulosic material-containing overcoating on the sensing element. Theuse of soluble cellulosic coating materials or soluble precursorsthereof allows for control of the amount of composition coated onto thesensing element and for a uniform and strong overcoating.

In one embodiment both the composition and the overcoating include anopaque agent. At least a portion of the opaque agent can be coated ontothe sensing element before the sensing element is contacted with thecomposition. In this embodiment, the present process further comprisescontacting the sensing element with an opaque agent to at leastpartially coat the sensing element with the opaque agent prior tocontacting the sensing element with the composition.

The composition preferably further includes at least one additionalcomponent in an amount effective to enhance the permeability (componentpermeability) of the overcoating. The additional component is preferablyremoved from the overcoating during the treating phase of the presentprocess, e.g., by an aqueous wash. Thus, the presently usefulpermeability enhancing agents are preferably water soluble or are madewater soluble while the overcoating itself is water insoluble. Thesepermeability enhancing agents preferably have no substantial detrimentaleffect on the cross-linked cellulosic coating material, on the sensingelement and on the opaque agent. Preferably, the permeability enhancingagent remains substantially unaffected during the present process untilit is removed to leave a more permeable overcoating relative to anovercoating produced without the permeability enhancing agent.

Any suitable permeability enhancing agent may be employed. Preferably,the permeability enhancing agent is soluble in the solvent used in thecomposition. This results in an overcoating with substantially uniformcomponent permeability. Particularly useful permeability enhancingagents are acylated glycerol and sugars, e.g., sucrose, in which theacyl groups contain about 1 to about 10 carbon atoms and mixturesthereof. Acetylated sucrose, e.g., sucrose octaacetate, and glyceroltriacetate are examples of these preferred permeability enhancingagents.

Although the cellulosic coating material itself may be included in thecomposition, it is preferred to use one or more soluble precursors ofsuch cellulosic materials. Such precursors should be soluble in thesolvent used in the composition and, during the treating phase of thepresent process, convert into a portion of the cross-linked cellulosicmaterial-containing overcoating. One particularly useful class ofcellulosic material precursors is the acylated celluloses in which theacyl groups include about 1 to about 10 carbon atoms. Acetylatedcellulose or cellulose acetate is a particularly useful cellulosicmaterial precursor.

The solvent used in the composition is chosen to allow the cellulosicmaterial or cellulosic material precursor to be soluble in thecomposition. This solvent is preferably nonaqueous, more preferablyorganic, in nature. Oxygen-containing hydrocarbon solvents such asketones, ethers and aldehydes can be used advantageously. Acetone isparticularly useful.

The treating phase or step of the present process preferably iseffective to cross-link the cellulosic material. In one embodiment, thetreating acts to form the overcoating by hydrolyzing the cellulosicmaterial or precursor thereof and cross-linking this hydrolyzed materialor precursor. Such a treating sequence is particularly effective whenthe composition contains a cellulosic material precursor.

The term "cross-linking" as used herein refers to a chemical reaction inwhich cellulosic molecules are reacted with multi-functional, e.g.,difunctional, compounds to join the cellulosic molecules together bybridges or cross-links derived from the multi-functional compounds orcross-linking agents. Hydrolyzing, the cellulosic material or precursor,e.g., using conventional techniques, makes the material or precursormore amenable to being cross-linked. Suitable cross-linking agents foruse in the present invention include ethylene glycol diglycidyl ether,butanediol diglycidyl ether, epichlorohydrin, 1,3, butadiene diepoxide,1,2,7,8 - diepoxy octane, 1,2,5,6-diepoxy cyclooctane, diethylene glycoldiglycidyl ether, other poly (i.e., di, tri, etc.) epoxides and mixturesthereof. Ethylene glycol diglycidyl ether is a particularly usefulcross-linking agent.

In another broad aspect, the present invention is directed to a probewhich comprises a plurality of sensing elements each of which is capableof sensing a different component in an aqueous medium. A plurality offirst overcoatings are included, each of which is located on a differentsensing element. These first overcoatings contain a water insoluble,component permeable, cross-linked cellulosic material and an effectiveamount of a first opaque agent. In addition, a second overcoating isprovided and is located on all of the first overcoated sensing elements.Preferably, the tips of the first overcoated sensing elements aresubstantially free of the second overcoating. This second overcoatingincludes a water insoluble, all component permeable, cross-linkedcellulosic material, and preferably an effective amount of a secondopaque agent. By "all component permeable" is meant that the secondovercoating is permeable to all components of interest, i.e., to allcomponents being sensed by the sensing elements is the probe, in theaqueous medium. This second overcoating provides additional strength tothe probe and acts to make the probe physically more smooth.

The final overcoating, whether it is the overcoating on a single sensingelement if no second overcoating is applied or the second overcoating ona bundle of sensors each of which contain a first overcoating,preferably has a blood compatible film formed on it. This film, which isoften composed of an antithrombogenic agent, acts to inhibit adverseeffects of having the sensor or probe in the blood stream.

These and other aspects and advantages of the present invention are setforth in the following detailed description and claims, particularlywhen considered in conjunction with the accompanying drawings in whichlike parts bear like reference numerals.

BRIEF DESCRIPTION OF THE DRAWINGS

This invention will be better understood when taken in conjunction withthe drawings wherein:

FIG. 1 is a side elevational view in section of a first sensor,including an overcoating of this invention;

FIG. 2 is a side elevational view in section of a second sensorincluding an overcoating of this invention;

FIG. 3 is a side elevational view in section of a third sensor includingan overcoating of this invention;

FIG. 4 is a side elevational view partially broken away, showing acomposite bundle of overcoated sensors; and

FIG. 5 is an end elevational view in section about the lines 5--5 ofFIG. 4.

DETAILED DESCRIPTION OF THE INVENTION

The above-noted patent applications all describe optical sensors andcomponents utilized with these sensors to measure the concentration orpartial pressure of a given component, in an aqueous medium, such asblood. Each of these sensors utilizes an optical indicator of thefluorescent dye type which is held in position on an optical surface ofan optical fiber. When the component to be sensed contacts or interactswith an optical indicator, an optical signal is generated which iscorrelatable to the amount of the component which is present.

In the illustrative embodiments of the above-noted patent applicationscertain fluorescent dyes are utilized.

The fluorescent dye of each individual sensing element is preferablycombined with a suitable matrix and/or other carrier. Thus, forinstance, in the above-noted patent applications a dye solubilized in asiloxane matrix is utilized for oxygen partial pressure-sensing; a dyeattached to a cellulose matrix is utilized for pH-sensing measurement;and a dye solubilized in aqueous microcompartments suspended in asiloxane matrix is utilized for carbon dioxide partial pressure-sensing.Each of these systems places the dye on the optical surface of anoptical fiber. An excitation signal is fed through the optical fiber tothe dye and a fluorescent signal emitted from the dye in response tointeraction of the dye with the component of interest is carried by theoptical fiber from the dye to suitable analyzing instrumentation. Thesensors can be sized to be of the size domain of the optical fiberitself.

Each of the above sensors can be advantageously augmented by includingan appropriate overcoating on the sensing element, i.e., the fluorescentdye. The overcoating enhances the performance of the sensors in severalways. It can serve as a protective membrane over these sensors toisolate the optical indicators from the environment which is beingsensed, for instance, the blood. Further it can serve to opticallyisolate the sensor from that environment or from a second sensor locatedin the vicinity of a first sensor. Additionally, it can provide asuitable surface on which further material can be located, for example,a film of antithrombogenic material. Also, it provides for anessentially smooth outer surface on the sensor which inhibitsthrombogenic reaction of the blood to the sensor. The overcoating of thesensor is permeable to the component being sensed. The overcoating isinsoluble in the aqueous medium, e.g., blood or other biological orbodily fluids, being tested so as to not contaminate the aqueous mediumbeing tested.

To enhance certain operating characteristics of the sensors, theovercoating includes an opaque agent effective to optically isolate thesensing element from the environment. This opaque agent can be suspendeddirectly in the overcoating material whereby the totality of theovercoating material itself becomes opaque, or the opaque agent can beplaced on the surface of the sensing element in a suitable carrier, withthe overcoating material being placed over the opaque agent.

The overcoating can be formed as a single layer or as multiple layerswhich are built up one on the other. It is generally preferred to keepthe overcoating material of a thickness sufficient to provide for properfunctioning of the overcoating as per the parameters outlined herein,but not of such a thickness as to substantially inhibit transfer of thecomponent species through the overcoating material in the time frame foruse of the sensor. Typically, the sensor should equilibrate with theaqueous medium being tested within a few minutes time, and as such,generally the overcoating material will be relatively thin so as toallow for equilibration within this time frame.

In one embodiment, a permeability enhancing agent is preferably utilizedin producing the overcoated sensors and probes of the present invention.For example, the permeability enhancing agent may be included insolution with a soluble coating material or a soluble precursor of acoating material in a composition which is contacted with and coats thesensing element or elements. The permeability enhancing agent ispreferably later removed from the overcoating, e.g., by washing with anaqueous wash medium. Typically, the permeability enhancing agent will bea water soluble compound, or be converted into a water-soluble compoundas for instance a compound having one or more hydroxyl groups, such as apoly-hydroxyl compound.

Multiple overcoatings can be utilized, as for instance a firstovercoating which serves in part, to hold an opaque agent in associationwith a sensor, and a second overcoating which serves in part, to providefor a smooth surface over a probe or bundle of sensors grouped together.The second overcoating may or may not include an opaque agent, althoughit is preferred to include an opaque agent since this aids inmanufacturing the present devices.

When a probe. i.e., a plurality or a bundle of sensors, is utilized, itis desirable to eliminate "cross talk" between the individual sensors.That is, it is desirable to inhibit signals, e.g., optical signals, fromone sensor influencing the signals of a second sensor. By providing anindividual overcoating on each sensor prior to forming the bundle ofsensors, cross talk between the sensors can be substantially reduced oreven eliminated. The bundle of microsensors can then be coated with afinal overcoating to provide a substantially smooth and uniform surface.The tip of each of the individual sensors is preferably not coated withthe final overcoating.

The overcoating of the present sensors and probes comprises a waterinsoluble, component permeable, cross-linked cellulosic material. Thematerial is permeable to a component to be sensed.

To facilitate formation of the cellulosic material containingovercoating, a composition including an organic solvent and an organicsolvent soluble precursor of cellulose, as for instance carboxylatedcellulose, is preferably utilized. Acetylated cellulose can beconveniently solvated in acetone. The acetone composition can be easilyand conveniently applied to the sensing element by simply depositing amicrodroplet of the composition on the tip of the sensor and allowingthe acetone to evaporate.

The cellulosic material or precursor thereof is preferably thenstrengthened by cross-linking. When acetylated cellulose is utilized asa cellulosic material precursor in forming a overcoating, the acetylgroups can be concurrently removed from the acetylated cellulose duringcross-linking by conducting a combination hydrolysis/cross-linkingreaction.

Preferred permeability enhancing agents are the acetylated polyols,glycerol and sucrose. This acetylated polyols are also soluble inorganic solvents, such as acetone. During the hydrolysis reaction of thecellulosic material on the sensing element, the acetylated polyol isalso hydrolyzed, allowing for removal of the polyol by elution into theaqueous treatment medium. Since the cellulose is not water soluble, whenthe polyol contained in the cellulose is exposed to an aqueous wash, thepolyol dissolves into the aqueous wash leaving behind a more permeablecellulose matrix of the overcoating material.

If a substituted precursor of the cross-linked cellulosic material isutilized, as for instance acetylated cellulose, the substituent groupsare preferably removed, e.g., before or at the time of thecross-linking. With acetylated cellulose, the acetyl substituent groupscan be removed in a facile manner with the use of a dilute basicsolution. Thus, for instance, a 1% sodium hydroxide solution can beused. If an acetylated permeability enhancing agent, such as glyceroltriacetate, is also utilized, concurrently with the hydrolysis of theacetyl groups of the cellulose, the acetyl groups of the glyceroltriacetate are also hydrolyzed. Cross-linking of the resultingcellulosic matrix can be carried out sequentially, e.g., after, orconcurrently with this hydrolysis.

Typically, the cellulose acetate is utilized as a mixture of di- andtri- acetyl cellulose. Such a mixture is commercially available and hasincreased solubility is acetone compared to neat triacetylatedcellulose.

The opaque agent is selected to be opaque to the particular wavelengthor wavelengths of light at which the sensor operates. These are selecteddepending upon the characteristics of the sensor as, for instance, theparticular dye utilized in the sensor.

Dye adsorptive opaque agents, such as carbon black and the like, areparticularly suitable for use in an opaque agent in certain sensors suchas the carbon dioxide sensor because of such agent's ability to block abroad band of optical wave lengths and to prevent the migration ofunwanted solvent soluble dyes from adjacent sensing elements during theovercoating process. An example is the prevention of the migration ofthe oxygen dye into the carbon dioxide sensor during the overcoatingprocess.

In a sensor, that has a sensing dye that is soluble in the compositionused to coat the sensing element, a dye nonadsorptive opaque agent isused since carbon black can cause depletion of the sensing dye from thesensor by dye extraction during the overcoating process. Copperphthalocyanine is a particularly effective dye non-adsorptive opaqueagent in the cellulosic overcoating composition for the oxygen sensingelement employing a fluorescent dye and for a bundle of sensors thatcontain such an oxygen sensing element.

The opaque agent, when used as a mixture with the coating material, issuitably suspended in the composition used to coat the sensing element,for example, utilizing a suitable homogenizer or the like. Thus, carbonblack or copper phthalocyanine can be directly suspended in thecomposition containing the soluble cellulosic material or solubleprecursor, and when the cellulosic material is cross linked, the carbonblack or copper phthalocynine is permanently dispersed and heldthroughout the totality of the matrix of the overcoating.

The Figures show several embodiments of sensors which incorporateovercoatings in accordance with this invention. For the purposes ofdescribing these figures, the actual fluorescent dye in a suitablematrix is referred to as a sensing element. Details as to thepreparation of these sensing elements is described in the above-notedpatent applications.

In FIG. 1 a first sensor 10 is shown. Sensor 10 includes an opticalfiber 12 having an optical surface 14. Positioned directly againstoptical surface 14 and down along the sides of the tip of optical fiber12 is a sensing element 16. Covering sensing element 16 is anovercoating 18. The overcoat 18 extends completely over sensing element16 and down along the side of optical fiber 12. Thus, the totality ofsensing element 16 is completely covered by overcoating 18. Sensor 10 ofFIG. 1 is typically utilized as a pH sensor as is described in patentapplication Ser. No. 917,912 noted above.

Overcoating 18 of sensor 10 includes carbon black (not separately shownor numbered) dispersed within the matrix of overcoating 18. Becauseovercoating 18 completely surrounds sensing element 16, sensing element16 has an opaque coating completely around it. This optically isolatessensing element 16 from the optical environment outside of overcoating18.

In FIG. 2 a second sensor 20 is illustrated. It includes an opticalfiber 22 having an optical surface 24. Positioned on the end of opticalfiber 22 is a sleeve 26 which holds an aliquot of a polymerized matrixcontaining sensing element 28 against optical surface 24. An overcoating30, having an opaque agent located therein, completely covers sensingelement 28 and sleeve 26. Sensor 20, having overcoating 30 thereon isused as either a carbon dioxide sensor or an oxygen sensor as describedin above-noted U.S. patent application Ser. No. 917,913. In the case ofthe carbon dioxide sensor, the preferred opaque agent is carbon black.In the case of the oxygen sensor, the preferred opaque agent is copperphthalocyanine.

In FIG. 3 a third sensor 32 is illustrated. It is similar to sensor 20of FIG. 2. It includes an optical fiber 34 having an optical surface 36thereon. A sleeve 38 is utilized to hold an aliquot of a sensing element40 against optical surface 36.

Sensor 32 differs from sensor 20 in that an opaque layer 42 is overlayedon sensing element 40. Opaque layer 42 is preferably formed ofdimethylpolysiloxane having an opaque agent, such as ferric oxide,dispersed therein. An overcoating 44 is now located over the totality ofthe end of optical fiber 34, sleeve 38 and opaque layer 42. Sincesensing element 40 is optically isolated by opaque layer 42, overcoating44 can be formed as a transparent layer. Alternatively, overcoating 44can also include an opaque agent.

FIGS. 4 and 5 show a sensor probe or bundle of individual sensorsgrouped together. Thus, in FIGS. 4 and 5 a sensor bundle 46 is shown. Itincludes three sensors, sensor 48, sensor 50 and sensor 52. These can bechosen to be one of any of the sensors shown in FIGS. 1, 2 and 3, orother sensors as might be desired for a particular application. In viewof this, explicit details of these sensors are not shown. They eachhowever include suitable optical fibers, 54, 56 and 58, respectively.Located on each of these optical fibers and covering the specificcomponents of the specific sensors 48, 50 and 52 are individualovercoatings 60, 62 and 64. Each of overcoatings 60, 62 and 64 includean opaque agent either in the overcoating material or another opaqueagent such as sensor 32 of FIG. 3, such that individual sensors 48, 50and 52 are optically isolated from one another to eliminate cross talkbetween these sensors.

Sensors 48, 50, 52 are located together at the bundle tip 66 of sensorbundle 46. Optical fibers 54, 56 and 58 are arranged in a triangulararrangement as is evident from FIG. 5. Fibers 54, 56 and 58 are heldtogether by a sleeve 68. Sleeve 68 is utilized to assist in introductionof sensor bundle 46 into its working environment, as for instanceintravenous positioning of sensor bundle 46.

Individual sensors 48, 50 and 52, having individual overcoating 60, 62,and 64, are positioned within sleeve 68 and a final bundle overcoating70 is then applied along the sides of bundle tip 66 without coating theend of bundle tip 66. Bundle overcoating 70 fills in the voids betweenindividual overcoatings 60, 62, and 64 forming a smooth surface atbundle tip 66 which inhibits thrombogenic reaction to sensor bundle 46.An epoxy coating 72 is positioned on sensor bundle 46 between the end 74of sleeve 68 and bundle overcoating 70.

As is evident from FIG. 4 bundle overcoating 70 forms a smoothtransition with epoxy coating 72 to sleeve 68. This substantiallyeliminates any pockets or voids that could provide a region of stasiswhere blood could coagulate. Finally, sensor bundle 46 is covered with ablood compatible coating of a antithrombogenic agent (not shown in thedrawings) that extends along the entire length of the bundle.

The following representative, non-limiting examples illustrate certainaspects of the present invention.

EXAMPLE 1

10 grams of acid free cellulose acetate available from Kodak Chemicals,Rochester, NY, having 39.9% acetyl content was dissolved in 100 grams ofanhydrous acetone.

EXAMPLE 2

To 10 grams of 10% cellulose acetate/acetone solution of Example 1,above, was added 0.2 grams of acid-free sucrose ocataacetate, availablefrom Sigma Chemicals, St. Louis, MO, and 0.4 grams of copperphthalocyanine available from Aldrich Chemical Co., Milwaukee, WI. Themixture was homogenized in a Virtis 45 high shear homogenizer for fiveminutes with the container positioned in a water bath for cooling duringhomogenization.

EXAMPLE 3

10 grams of acid-free sucrose ocataacetate was dissolved in 100 grams ofanhydrous acetone.

EXAMPLE 4

A thin layer of the cellulose acetate/sucrose octaacetate/copperphthalocyanine mixture from Example 2, above, was applied to the end ofthe oxygen sensor equivalent to sensor 20, above. The coating mixturewas transferred to the sensor utilizing a tiny rod as a carrier. The rodwas dipped into the cellulose acetate/sucrose octaacetate/copperphthalocyanine mixture to adhere a microdroplet of this mixture on theend of the rod. The end of the rod was then dipped into the sucroseoctaacetate/acetone solution of Example 3 to further wet the microdropjust prior to application to the sensor to minimize the effect ofevaporation before and during the application process. After the coatingwas applied, the solvent was allowed to evaporate. The overcoating wasthen hydrolyzed and cross-linked by immersion in an aqueous solutioncontaining 1.0% by weight sodium hydroxide and 5% by weight ethyleneglycol diglycidyl ether for thirty minutes. After hydrolysis andcross-linking, the overcoated sensor was rinsed in an aqueous solutioncontaining 1% by weight sodium bicarbonate and 5% by weight glycerol.

EXAMPLE 5

To 10 grams of the 10% by weight cellulose acetate/acetone solution ofExample 1 was added 0.4 grams of carbon black. The mixture washomogenized as in Example 2, and applied to a carbon dioxide sensor,hydrolyzed and cross-linked as in Example 4. The sensor is rinsed as inExample 4.

EXAMPLE 6

In a like manner to Example 4, an overcoating was applied to a pH sensorsimilar to sensor 10, above, except that the overcoating compositioncontained 4% by weight carbon black instead of copper phthalocyanine and10% by weight triacetin instead of sucrose octaactate. In addition, theacetone resolvation solution contained triacetin instead of sucroseoctaacetate.

EXAMPLE 7

In a like manner to Example 6, an overcoating was applied to the pHsensor similar to sensor 10, above, except that the hydrolysis andcross-linking steps were carried out separately. First the overcoat washydrolyzed by immersion in a 1% by weight sodium hydroxide aqueoussolution. Then it was cross-linked by immersion in an aqueous solutioncontaining 1.0% by weight of sodium hydroxide and 5% by weight ofethylene glycol diglycidyl ether.

EXAMPLE 8

Example 4 with a further overcoating of cellulose acetate utilizing thecellulose/sucrose octaacetate solution prepared as per Example 2, withthe exception that copper pythalocyanine was omitted. After applicationof the cellulose acetate/acetone solution to the oxygen sensor, theacetone was allowed to evaporate and the cellulose acetate was thenhydrolyzed and cross linked as per Example 6, above.

EXAMPLE 9

A carbon dioxide sensor, an oxygen sensor and a pH sensor were combinedin a sleeve so as to locate the sensors together in a bundle. Using themixture of Example 2 and the procedure of Example 4, a thin overcoatingwas applied on the side of the bundle. Care was taken to prevent buildupof the overcoating at the bundle tip in order to hold the overcoatingthickness at the tip to a minimum. However, sufficient coating materialwas utilized to fill in the spaces between the individual sensors.

EXAMPLE 10

In a like manner to Example 9, an overcoating containing copperphthalocyanine in place of carbon black was formed on a sensor bundlecontaining an oxygen sensor, a carbon dioxide sensor and a pH sensor.

While the present invention has been described with respect to variousspecific examples and embodiments, it is to be understood that thepresent invention is not limited thereto and that it can be variouslypracticed within the scope of the following claims.

What is claimed is:
 1. A sensor comprising a sensing element capable ofsensing a component in an aqueous medium and an overcoating at leastpartially covering said sensing element, said overcoating comprising awater insoluble, component permeable cellulosic material cross-linkedwith one or more multi-functional cross-linking agents and an effectiveamount of an opaque agent.
 2. The sensor of claim 1 wherein said sensingelement is selected from the group consisting of optical indicators andelectro-chemical indicators.
 3. The sensor of claim 1 wherein, saidsensing element is selected from the group consisting of opticalindicators.
 4. The sensor of claim 1 wherein said sensing element isselected from the group consisting of fluorescence indicators andabsorbance indicators.
 5. The sensor of claim 1 wherein said sensingelement is selected from the group consisting of fluorescenceindicators.
 6. The sensor of claim 5 wherein said opaque agent is a dyeadsorptive opaque agent.
 7. The sensor of claim 6 wherein said opaqueagent is a dye adsorptive opaque agent and said dye adsorptive opaqueagent is carbon black.
 8. The sensor of claim 6 wherein said sensingelement is a fluorescence indicator capable of sensing carbon dioxide.9. The sensor of claim 5, wherein said opaque agent is a dyenon-adsorptive opaque agent.
 10. The sensor of claim 9 wherein said dyenon-adsorptive opaque agent is selected from the group consisting offerric oxide and metallic phthalocyanines.
 11. The sensor of claim 10wherein said dye non-adsorptive opaque agent is a metallicphthalocyanine and the metallic portion of said phthalocyanine isselected from the group consisting of copper, iron, cobalt, lithium,magnesium, nickel, zinc, vanadium, manganese, sodium and mixturesthereof.
 12. The sensor of claim 9 wherein said sensing element is afluorescence indicator capable of sensing oxygen.
 13. The sensor ofclaim 12 wherein said dye non-adsorptive opaque agent is copperphthalocyanine.
 14. The sensor of claim 1 wherein said aqueous medium isa bodily fluid.
 15. The sensor of claim 14 which further comprises ablood compatible film located on the outside surface of saidovercoating.
 16. The sensor of claim 1 wherein said aqueous medium isblood.
 17. The sensor of claim 1 wherein said cross-linked cellulosicmaterial is cross-linked cellulose.
 18. The sensor of claim 1 whereinsaid component is selected from the group consisting of gases, hydrogenions, other electrolytes and glucose.
 19. The sensor of claim 1 whereinsaid component is selected from the group consisting of gases andhydrogen ions.
 20. The sensor of claim 1 wherein said component isselected from the group consisting of oxygen, carbon dioxide andhydrogen ions.
 21. An overcoated sensing element produced in accordancewith the process comprising:contacting a sensing element with acomposition containing a solvent and a solvent soluble cellulosiccoating material or a solvent soluble precursor of said cellulosiccoating material to form a composition coated sensing element; andtreating said composition coated sensing element to form an overcoatingon said sensing element, said overcoating being permeable to a componentof interest, wherein said composition further includes a permeabilityenhancing agent in an amount effective to enhance the componentpermeability of said overcoating formed.
 22. An overcoated sensingelement as defined in claim 21 wherein said permeability enhancing agentis substantially removed from said composition coated sensing elementduring said treating step.
 23. An overcoated sensing element as definedin claim 22 wherein said permeability enhancing agent is water solubleand said treating step comprises contacting said composition coatedsensing element at conditions effective to form a cross-linkedcellulosic material on said sensing element and contacting said sensingelement containing said cross-linked cellulosic material with an aqueousliquid at conditions effective to substantially remove said permeabilityenhancing agent.
 24. An overcoated sensing element as defined in claim23 wherein said composition coated sensing element is contacted atconditions effective to hydrolyze at least a portion of said cellulosicmaterial on said sensing element, and said sensing element containingsaid hydrolyzed cellulosic material is contacted with at least onecross-linking agent at conditions effective to form a cross-linkedcellulosic material on said sensing element.
 25. A probe capable ofsensing a plurality of different components in an aqueous medium whichcomprises:a plurality of sensing elements each of which is capable ofsensing a different one of said components in said aqueous medium; aplurality of first overcoatings each of which is located on a differentone of said sensing elements and each of which comprises a waterinsoluble, component permeable cellulosic material cross-linked with oneor more multi-functional cross-linking agents and an effective amount offirst opaque agent; and a second overcoating located on all said firstovercoated sensing elements and comprising a water insoluble, allcomponent permeable cellulosic material cross-linked with one or moremulti-functional across-linking agents.
 26. The probe of claim 25wherein said sensing elements are selected from the group consisting ofoptical indicators and electro-chemical indicators.
 27. The probe ofclaim 26 wherein said aqueous medium is a bodily fluid.
 28. The probe ofclaim 25 wherein said sensing elements are selected from the groupconsisting of optical indicators.
 29. The probe of claim 25 wherein saidsensing elements are selected from the group consisting of fluorescenceindicators and absorbance indicators.
 30. The probe of claim 25 whereinsaid sensing elements are selected from the group consisting offluorescence indicators.
 31. The probe of claim 30 wherein each of saidfirst opaque agents is a dye adsorptive opaque agent.
 32. The probe ofclaim 31 wherein said second overcoating further comprises an effectiveamount of a second opaque agent and wherein said second opaque agent isa dye non-adsorptive opaque agent.
 33. The probe of claim 32 whereinsaid dye adsorptive opaque agent is carbon black and said dyenon-adsorptive opaque agent is copper phthalocyanine.
 34. The probe ofclaim 30 wherein each of said first opaque agents is a dyenon-adsorptive opaque agent.
 35. The probe of claim 25 wherein saidsecond overcoating further comprises an effective amount of a secondopaque agent.
 36. The probe of claim 25 wherein said aqueous medium isblood.
 37. The probe of claim 25 wherein said cross-linked cellulosicmaterial is cross-linked cellulose.
 38. The probe of claim 25 whereinsaid components are selected from the group consisting of gases,hydrogen ions, other electrolytes and glucose.
 39. The probe of claim 25wherein said aqueous medium is blood and said probe further comprises ablood compatible film located on said second overcoating.